New Evidences: Acidity Theory of Atherosclerosis

"Carlos, your thesis on stress, acidic environment and CHD is brilliant. Particularly impressive is how you relate reduced pH to increased oxidation of LDL, which increases its atherogenicity" by David M Diamond, PhD*, THINCS forum on June 22, 2011.
*Professor Depts of Psychology and Molecular Pharmacology and Physiology, University of South Florida.

Sunday, January 22, 2017

New Book (2016)

“Fat and Cholesterol Don’t Cause Heart Attacks

And Statins Are Not The Solution”

Edited by Prof. Dr. Paul Rosch this book is a tribute to Dr. Uffe Ravsnkov, an extraordinary and tireless researcher, founder of “The International Network of Cholesterol Skeptics (THINCS)”. Among other bookstores you can find this book at https://www.amazon.com/Cholesterol-Cause-Attacks-Statins…/…/Uffe Ravsnkov’s monograph, “The Cholesterol Myths”, can be read free of charge, at https://www.smashwords.com/books/view/486704The present book contains 17 chapters written by a select group of medical researchers and scientists. I’m honored to participate in this tribute to Uffe Ravsnkov.My chapter is entitled “Stress as Cause of Atherosclerosis – The Acidity Theory”.During the last year I have presented an article about the acidity theory of atherosclerosis, developed in 2006, addressing its history, pathophysiology, therapeutics, risk factors and external markers. There I also have wrote about individuals with lower degree or absence of atherosclerosis, and on the reversion or lower progression of atherosclerosis through the use of sympatholytic drugs and by stress reduction approaches (http://goo.gl/AejGAV). In this book (Chapter 10) I extend the discussion about the etiology of the Acidity Theory of Atherosclerosis, aside to present new risk factors and other diseases associated to atherosclerosis, under its point of view. Also, I brought up for discussion the inverse association between cancer and atherosclerosis, confirmed by recent studies*. Follows the abstract:AbstractThe link between stress and atherosclerosis is well-known with many studies and postulations in this regard. However, there is a general unawareness that stress can induce hyperlactatemia and lactic acidosis, because this relationship has been little discussed in medical science. The influence of adrenaline on lactic acid production was first noticed by Carl Ferdinand Cory in 1925. The heart is an organ of high metabolic activity – that cannot rest as other body muscles, being susceptible to drops in pH during ischemia and hypoxia. The chronic elevated catecholamine release, triggered by sympathetic dominance, may accelerate the myocardial glycolysis leading to significant increase in lactate production. Risk factors for atherosclerosis like hypertension, diabetes, cigarette smoking, stress conditions and high carbohydrate diets are linked to autonomic dysfunction. These risk factors present as well an increased concentration of lactate in plasma. Blood lactate is also associated with carotid atherosclerosis. Plasma lipid abnormalities and myocardial lactate production were significantly associated with subsequent arteriographic progression. The amount of lactate released by the myocardium has been shown to be related to the severity of coronary artery disease. Reduced pH increases the oxidation of low-density lipoprotein that is considered to have a significant role in atherogenesis. According to the acidity theory of atherosclerosis the acidosis evoked by sympathetic dominance or continuous stress leads to changes in shear stress, the final stage in the development of atherosclerotic lesions. The importance of mechanical forces such as those derived from changes in hemodynamic shear stress, as a decisive factor for atherosclerosis, was advocated by Meyer Texon since1957.* You can also see the studies confirming about the inverse association between cancer and atherosclerosis at our article Cancer, Atherosclerosis and Sympathetic Dominance, Positive Health Online, issue 223, 2015

Thursday, February 7, 2013

Current evidence from pathological, clinical and
epidemiological studies indicates that there is an association of Alzheimer’s
disease (AD) and atherosclerotic disease, through a chronically lowering brain
hypoperfusion.

Indeed, recent studies have shown that severe increase
of carotid intimal medial thickness may be considered as a marker factor of progression
of the cognitive decline in AD, and that intervention to reduce atherosclerosis
may help to prevent onset of vascular dementia (VaD) and AD (1,2,3)

Anyway, we should take in account that vascular
dementia and AD have different pathological origins with AD linked to low blood
pressure and vascular dementia to high blood pressure (4).

Jack C de la Torre, one of the developers of the
vascular hypothesis (5), in a recent study (6) has implicated many other possible
cardiovascular risk factors beyond coronary artery disease, in the development
of cognitive impairment preceding AD. Among these risk factors he cites: atrial
fibrillation, thrombotic events, hypertension, hypotension, heart failure, low
cardiac index and vascular pathology.

In his list sounds paradoxical the inclusion of
hypertension as one of the cardiovascular risks factors responsible for the
development of cognitive decline before AD, taking hypoperfusion as the key
factor. Although, he argues that many studies have implicated impaired cognitive
function to hypertension in geriatric patients and that is known for some time
that hypertension in the elderly is a potential risk factor for AD.

De la Torre says that what is still not clear is precisely how
hypertension increases the incidence of AD, particularly in those not treated
with antihypertensives. His theory is that chronic brain hypoperfusion
generated by increased vascular resistance from hypertension may be a key
factor linking high blood pressure and AD.

However, even that various studies have reported that
high blood pressure in midlife may increase the risk for late-life cognitive
impairment, white matter lesions, clinical dementia and neuropathological
markers of AD (7, 8), there are some contradictory findings about the role of
hypertension in AD, like:

a)A meta-analysis of
longitudinal studies has shown no significant difference
in incidence of AD between subjects with and without antihypertensive
medication use (9).

b)A review by Cochrane Database tells that there is
no convincing evidence from the trials identified that blood pressure lowering
in late-life prevents the development of dementia or cognitive impairment in
hypertensive patients with no apparent prior cerebrovascular disease (10).

c)The prevalence of midlife
hypertension is lower in patients with AD compared to subjects without AD (11)

What sparked my interest regarding Alzheimer’s disease and its
association with atherosclerosis / cardiovascular disease was a recent report
by Medical News Today (12) informing that the use of beta-blockers for the
treatment of hypertension resulted in fewer Alzheimer’s type brain lesions on
autopsy than the use of other hypertensive medications.

This study involved
774 elderly Japanese-American men who took part in the Honolulu-Asia Aging
Study (8). Autopsies were performed after the death of the participants. Of the
774 men, 610 had high blood pressure or were being treated with medication for
high blood pressure. Among those who had been treated (about 350), 15 percent
received only a beta blocker medication, 18 percent received a beta blocker
plus one or more other medications, and the rest of the participants received
other blood pressure drugs.

They found that all
types of blood pressure treatments were clearly better than no treatment.
However, men who had received beta blockers as their only blood pressure
medication had fewer abnormalities in their brains compared to those who had
not been treated for their hypertension, or who had received other blood
pressure medications. The brains of participants who had received beta blockers
plus other medications showed an intermediate reduction in numbers of brain
abnormalities.

These included two
distinct types of brain lesion: those indicating Alzheimer’s disease, and
lesions called microinfarcts, usually attributed to tiny, multiple,
unrecognized strokes. Study participants who had taken beta blockers alone or
in combination with another blood pressure medication had significantly less
shrinkage in their brains (13, 14).

My interest on the matter has even increased when I read the interview
by Dr. White, one of the authors, to Heartwire (15):

-- Speculating on the mechanism, White noted
that beta-blockers reduce pulse rate, which might have an effect on
small-vessel microinfarcts in the brain. "Lifelong exposure of the pulse
pressure in the brain might cause some damage," he said. "While we
thought beta-blockers may reduce brain microinfarcts, which they did, we
actually saw a larger reduction in the Alzheimer's-type lesions, which we had
not expected. This is somewhat of a mystery at present and may be a chance
finding. But if it is a real effect, I would think it was something to do with
autonomic function." White suggested that a reasonable next step could be
to test this hypothesis in mice genetically engineered to produce these
Alzheimer's lesions. "If we treat these mice with beta-blockers and they
develop fewer lesions, then we will know that it is an effect of the
drugs," he commented. –

Moreover, I see some convergence between White’s interpretations and our
concepts that the autonomic nervous system dysfunction, with sympathetic
dominance, is the primary factor in the cascade of events leading to
atherosclerosis, according the acidity theory developed by us in 2006. On the
other side beta-blockers have sympatholytic effects that led to a reduction in the
progression of atherosclerotic plaques in many studies. The use of sympatholytics
might offer some benefits to AD in this sense (16).

So, we searched for papers about autonomic
dysfunction and beta-blockers use in Alzheimer’s disease.

Regarding autonomic dysfunction I found many studies
showing this relationship, with the indication of increased sympathetic activity and decreased
parasympathetic activity in patients with Alzheimer’s disease (17-25). I also noticed about a recent hypothesis stating that
elevated endogenous brain norepinephrine may be an etiological factor in some
cases of AD, both before and during disease progression (26).

In fact, a recent study found
that baroreflex function is reduced in Alzheimer’s disease (27). Impaired baroreflex sensitivity may activate the
sympathetic nervous system (28).

The first study demonstrating some benefit of beta-blockers use in
senile dementia occurred when six patients exhibiting severe disruptive
behavior were effectively treated with propranolol which controlled this
condition in all cases, without the need of inducing general sedation (29).

More recently, a large population-based study of persons 65 years and
older reported that the use of antihypertensive medications, including
beta-blockers, significantly lowered the risk of AD (30). In a subsequent
analysis of the Cache Count study of individuals with incident AD, the
participants taking beta-blockers – mostly patients with angina - experienced
40% decrease in rate of functional decline compared to those not taking
beta-blockers (31).

In fact there is an indication
through a recent retrospective database study about a possible protective effect
of some antihypertensive agents (beta blockers and ACE inhibitors) on the development
of dementia (32)

Also, animal experiments using the beta-blocker carvedilol found that it
interferes with neuropathologic, biochemical and electrophysiological
mechanisms underlying cognitive deterioration in AD supporting the potential
development of carvedilol as a treatment for AD. In other publication the same
group says that their results suggest that carvedilol reestablishes basal
synaptic transmission, enhances neuronal plasticity and suppresses neuronal
hyper-excitability in mice (33, 34).

Despite its beneficial effects in reduction of the progression of
atherosclerotic plaques and possible positive actions directly in the brain,
the use of beta-blockers may carry some risks that were reported in recent
studies, for example:

a)The effect of betablockers as a
treatment for primary hypertension has been questioned. In a meta-analysis
study published at Lancet Journal in 2005 the authors say that the effect of
betablockers compared to placebo is less than optimum, with no difference for
myocardial infarction but with a raised risk of stroke (35). By the way,
hypertension is a highly prevalent risk factor for stroke.

b)A recent study confirm that the
use of beta blockers do not appear to be of any benefit in three distinct
groups of stable outpatients: those with coronary artery disease but no history
of MI; those with a remote history of MI (one year or more); and those with
coronary risk factors only (36).

c)Moreover in a randomized trial
study published in Lancet Journal in 2008 the authors say that there were more
deaths in the metoprolol group than in the placebo group in patients undergoing
non-cardiac surgery (129 versus 97 patients) (37).

d)Finally, a new
meta-analysis suggests that beta-blockers have little effect in heart-failure
patients with atrial fibrillation (38). Beta-blockers have been a cornerstone
of the treatment of heart failure and are recommended for both HF and AF
treatment, albeit for different indications. In HF recommendations,
beta-blockers are indicated as standard therapy for all
patients to reduce morbidity and mortality, paradoxically, even in systolic
heart failure that is caused by reduced cardiac contractility that results in
inadequate cardiac output.

So, while betablockers may be
seen useful in atherosclerosis and in other diseases its poor results in the clinical
situations cited above might be related to their effects of generalized
hypocontractility, as advocated by Mesquita and colleagues since 1979 (39).

The decreased myocardial contractility caused by the use of
beta-blockers deserves further researches not only to confirm if the negative
inotropism is the real culprit for the poor results achieved by these drugs as
well tolook for other sympatholytic
drugs that will help the brain without depress the heart.

Carlos Monteiro

P.S.:

An alternative sympatholitic that should deserve a further research for the treatment of hypertension and
atherosclerosis should be digoxin at low dosage that might offer some beneficial
effect in lowering the risk for dementia and AD (16).

Digoxin that was used effectively in heart failure, atrial fibrillation,
in some arrhythmias and in coronary myocardial disease would in our view help
the brain without depress the heart. By the way,digoxin treatment at low doses (< or = 0.125 mg/d) is
likely to result in low serum concentrations of 0.5 - 09 ng/ml (40). Gheorghiade
M et al, in a retrospective analysis of data from the DIG trial also have
indicated a beneficial effect of digoxin on morbidity and no excess mortality
in women at serum concentrations from 0.5 to 0.9 ng/ml, whereas serum
concentrations > or =1.2 ng/ml seemed harmful (41)

Saturday, June 23, 2012

Many studies are
suggesting that high-carbohydrate diets, particularly in the form of
high-glycemic index load, may activate the sympathetic nervous system with
deleterious effects to human health (1). On the other side protein or fat
ingestion have no significant sympathoexcitatory effect (2,3,4).

Also, the sympathetic activation have been
linked in several studies to obesity, hypertension, insulin resistance,
diabetes, and even atherosclerosis (5, 6, 7)

If the above studies are right, continuing
to give support to high carbohydrate diets is both a wrong choice as well a bad
advice.

Wednesday, May 23, 2012

The Spanish EPIC cohort study (European Prospective Investigation into Cancer), published in 2010, including 15630 men and 25808 women, has concluded that alcohol intake (moderate, high and very high consumption) in men aged 29–69 years was associated with a more than 30% lower CHD incidence (1). Reading an old article by Leary (2) from 1935, I see that his interest in arteriosclerosis arose out of information that a class persons suffering from alcoholism appeared to show a lesser degree of atherosclerosis than their ages would justify. So, I have searched for recent papers that could confirm this relationship and found a study from 1997 comparing a cohort of alcoholics who underwent a medico-legal autopsy during a five-year period with non-alcoholic controls who did not differ from the alcoholics in selection criteria. This study has show in the examinations, that alcoholic men and old women had a significantly lower degree of atherosclerosis in the coronary arteries (3)A paper published in 2002 may have the answer to why alcoholics have a significantly lower degree of atherosclerosis in the coronary arteries and risk for coronary heart disease (4). Regarding this paper, a release from EurekAlert (5), with an interview by William Lovallo, one of the authors, told that:“Before testing alcoholics for their responses to a public-speaking task, researchers first needed to establish if their sympathetic nervous system was able to respond at all. "This would tell us if their blunting was specific to psychological stressors like public speaking," said Lovallo, "or due to a generalized autonomic deficit." He and his colleagues examined 20 alcohol-dependent subjects, abstinent for 21 to 28 days, and 10 age-matched nonalcoholics. All subjects were males between the ages of 22 and 55 years. The researchers used impedance cardiography and dinamap blood pressure monitoring to assess the participants' heart rate, stroke volume, cardiac output, total peripheral resistance, mean arterial pressure, systolic blood pressure, and diastolic blood pressure during orthostasis and public speaking. Self-reported mood was also assessed during these two tasks. Cardiovascular responses to orthostasis were similar for the two groups. However, the alcoholics had blunted heart-rate responses to public speaking even though they reported similar anxiety responses to the nonalcoholics. This suggests a disconnection between perception of threat and resulting physiological responses among the alcoholics. "The similar cardiovascular responses to orthostasis among the alcohol-dependent patients indicate that their autonomic nervous systems were working normally," said Lovallo. "Yet when we asked them to prepare and memorize a short speech and then deliver the speech to a video camera, the patients reacted with little or no change in heart rate, and of course, they failed to have a cortisol response. The patients reacted as if the social challenge of public speaking had no special meaning for them. So, the sympathetic nervous system in the patients looked normal, but their response to a psychological stressor was almost absent. When faced with a socially meaningful stressor, neither part of their fight-flight mechanism was working."These results support the concept of the acidity theory where sympathetic predominance is the primary factor leading to atherosclerosis (6)Carlos Monteiro1. L Arriola, P Martinez-Cambor, N Larranaga, M Basterretxea. Alcohol intake and the risk of coronary heart disease in the Spanish EPIC cohort study. Heart 2010;96:124-130 doi:10.1136/hrt.2009.173419
2. Leary T. Atherosclerosis, the important form of arteriosclerosis, a metabolic disease. Vol 104, N7. JAMA, 19353. Thomsen JL. Atherosclerosis in alcoholics. Forensic Sci Int. 1995 Oct 30;75(2-3):121-31 and in Ugeskr Laeger. 1997 Feb 3;159(6):757-.604. Tera L. Panknin, Stacey L. Dickensheets, Sara J. Nixon, William R. Lovallo. Attenuated Heart Rate Responses to Public Speaking in Individuals With Alcohol Dependence. Alcohol Clin. Exp. Res. 2002 Jun; 26 (6): 8415. Alcoholics have 'blunted' responses to psychological stressors such as public speaking. Public release date: 17-Jun-2002 at http://www.eurekalert.org/pub_releases/2002-06/ace-ah061002.php6. Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis, 2008 at http://www.infarctcombat.org/AcidityTheory.pdf

Thursday, March 8, 2012

By Zoe V. Harcombe* Review at AmazonThis must be the academic equivalent of the "Collection of short stories" format so popular in the fiction world. It's a collection of articles, all different, but related by a common theme - heart disease.

I really enjoyed the format - it gives a taste of each topic without going into massive detail on each. The comprehensive references point the way if you want to know more about any particular factor in coronary artery disease. I never knew that the condition of having Down syndrome seems to have some protective properties when it comes to heart disease. What about the role of bacteria, or lactic acid? Is erectile dysfunction trying to tell us something? More familiar topics, such as smoking and stress, are covered but in a really new and often surprising way. I lost count of the number of times I learned something new or saw a well known topic covered in an innovative way.

I like the way the author thinks and challenges everything and makes connections between seemingly unrelated things. I also liked the inputs from colleagues - for example David Diamond's contribution to the article "Is LDL unquestionably and unequivocally a causal risk factor for heart attack?" The role of glucose (not fat) in the working of the body was fascinating and should be far more widely known.

You cannot fail to learn something if you read this book. If you are interested in our number one killer of humans - men especially - this is well worth your time.

Infarct Combat Project

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Book Acidity Theory of Atherosclerosis - New Evidences, 2012

Book Myogenic Theory of Myocardial Infarction, 1972

About Me

An independent researcher and scientist from Brazil.
Disciple and follower in the scientific plan of Dr. Quintiliano H. de Mesquita, who has developed the myogenic theory of myocardial infarction and other pioneer contributions to medical literature.
President of Infarct Combat Project (http://www.infarctcombat.org) an international organization that fights heart disease through information, research and education; non-official member of "The International Network of Cholesterol Skeptics (THINCS –http://www.thincs.org); Fellow of the American Institute of Stress (http://www.stress.org) and
member from the honorary board of "Weston A. Price Foundation" (http://www.westonaprice.org/) that is dedicated to explore the scientific validation of dietary, agricultural and medical traditions throughout the world.
In 2006 he has developed the acidity theory of atherosclerosis which gives a new explanation for the pathophysiological process of coronary artery disease.
He is the author of the book "Following the steps of a genius - A saga in medicine" with the first pages in English published at http://www.wattpad.com/1173810-following-the-steps-of-a-genius-a-saga-in-%20medicine